The general objectives of this investigation are concerned with carrying out an in-depth study of the chemical and biotransformation of the anticancer drug 4'-(9-acridinylamino)-methanesulfon-m-anisidide (NSC 249992, m-AMSA) and selected related compounds in experimental animals. It is a goal of these studies to determine whether bioactivation of m-AMSA occurs in vivo and to assess whether bioactivated intermediates are responsible for the antitumor activity of the drug. Chemical kinetic studies to characterize the reaction sequence in the hydrolytic degradation of m-AMSA will be carried out. A study of the reactions of the intermediates in the reaction sequence with selected nucleophiles which are cellular constituents will be undertaken. In vivo metabolism studies will be accomplished by (a) administering the unlabeled and radiolabeled drug to rats and dogs, (b) isolating the major metabolites from urine, bile and plasma, (c) spectrally characterizing the major metabolites of the drug, and (d) quantitating the metabolites in selected biological fluids. In vitro metabolism studies employing tissue homogenates and particularly, subcellular fractions will be performed. The structures of the chemical and biotransformation intermediates will be used as leads in studies concerned with the synthesis of selected congeners of m-AMSA. It is expected that these studies will provide information relating to the mode of action of m-AMSA.